Making science accessible for blind and low-vision people, and those with diverse needs.

The May-June 2024 issue of Immunology & Cell Biology contains an Immunology Futures Special Feature on Disability Inclusion in Science. Diverse groups do better in science, yet individuals with disabilities face barriers to accessing education and opportunities within scientific disciplines. The Monash Sensory Science program, led by Professor Jamie Rossjohn and legally blind artist in residence Dr Erica Tandori, has transformed the accessibility for those with blindness, low vision and diverse needs (BLVDN) to experience biomedical data visualization through the form of multisensory scientific communication. The Monash Sensory Science Exhibition, first hosted in 2018 with the support of Monash University and the Australian Research Council, utilizes tactile multisensory and multimodal artworks, interactive displays and multisensory science books for BLVDN participants. In this Special Feature, scientists and researchers involved in the 2023 Autoimmunity Monash Sensory Science Exhibition discuss the novel models and displays designed to improve the scientific understanding of complex autoimmune diseases including rheumatoid arthritis, lupus, celiac disease, psoriasis and type 1 diabetes. This Special Feature aims to inform the inclusive teaching of immunology and raise discussions of how to improve access to all within our scientific institutions.

Art, science and inclusion: multisensory Sciart of immunology for blind, low-vision and diverse-needs audiences.

Art is a powerful tool for conveying scientific discovery. Despite the perceived gap between art and science, as highlighted by CP Snow and others, examples of art communicating science can be found in the ancient world, the Renaissance and contemporary data visualization, demonstrating an enduring and historic connection. However, much of science relies on visual elements, excluding those with blindness, low vision and diverse needs, resulting in their low representation in STEM discourse. This paper introduces a novel science and art collaboration in the form of an exhibition program exploring the concepts of Immunology and Biomedicine to blind and vision-impaired audiences, capitalizing on the lived experience of a legally blind artist. Employing multisensory design, art and co-creation methodologies, it transcends traditional vision-based science communication, showcasing the potential for multisensory art to bridge the gap at the intersection of science and inclusion.

Inclusive multisensory science and immunology books for blind, low-vision and diverse-needs audiences.

This paper presents interdisciplinary research exploring the development of inclusive multisensory science books, communicating immunology data for blind, low-vision and diverse-needs audiences. The research adopted an inductive theory-building approach, practice-based art methods and music and design methods, leveraging the lived experience of a legally blind artist. The research also involved designers and scientists in a cocreation process, producing books that incorporate tactile artworks, Braille-inspired protein models, image sonification and interaction. Two multisensory book titles, "The Heroes Within You: A Multisensory Exploration of Infection and Immunity" and "My Goodness: A Multisensory Exploration of Nutrition and Immunity", were developed for the Monash Sensory Science 2023 Exhibition Day. The books offer an innovative way to make science and art more accessible and engaging, addressing the limitations of traditional museum methods. Feedback from audiences has been positive, emphasizing the fascination, sensory engagement and ease of understanding. This paper highlights the potential for an interdisciplinary and inclusive approach to science and art, demonstrating the value of multisensory books as tools for science communication. The findings highlight the positive reception of this novel approach and suggest its potential for broader applications, promoting inclusivity and accessibility.

Clinical manifestations and visual outcomes associated with ocular toxoplasmosis in a Brazilian population.

Ocular toxoplasmosis is the leading cause of posterior uveitis worldwide. We conducted an observational study of 262 consecutive individuals (n = 344 eyes) with ocular toxoplasmosis who were followed over a 34-month period. Most subjects were T. gondii IgG + /IgM- (n = 242; 92.4%; 317 eyes), and 140 eyes (40.7%) had active lesions. For eyes in which retinal lesions were active at recruitment and best-corrected visual acuity (BCVA) could be measured (n = 133), 21.0% (n = 28) remained blind (BCVA below 20/400) after inflammation resolved. In these eyes, atypical ocular toxoplasmosis (OR 4.99; 95% CI 1.14-22.85; p = 0.0330), macular lesion (OR 9.95; 95% CI 2.45-47.15; p = 0.0019) and any complication (OR 10.26; 95% CI 3.82-30.67; p < 0.0001) were associated with BCVA below 20/200. For eyes with only inactive lesions at recruitment and BCVA measured (n = 178), 28.1% (n = 50) were blind. In these eyes, having at least one lesion larger than one disc-diameter (OR 6.30; 95% CI 2.28-22.46; p = 0.0013) and macular lesion (OR 5.69; 95% CI 2.53-13.54; p < 0.0001) were associated with BCVA below 20/200. Older age (OR 1.02; 95% CI 1.00-1.05; p = 0.0493) and active disease at presentation (OR 4.74; 95% CI 1.95-12.91; p = 0.0011) were associated with recurrences. Additional clinical attention should be directed towards patients with risk factors for poor visual outcome.

Infliximab-induced optic neuritis.

Antitumour necrosis factor alpha agents are important treatments in many inflammatory conditions including rheumatoid arthritis, psoriatic arthritis and the inflammatory bowel diseases. However, there have been case reports of optic neuritis and other demyelinating diseases as complications of these agents. This case report presents a patient with ulcerative colitis on infliximab who presented with sudden onset mono-ocular visual field loss and highlights the diagnosis and management of infliximab-induced optic neuritis.

Varicella zoster virus (VZV) oculomeningoencephalomyeloradiculitis: a previously undescribed constellation.

A 53-year-old immunocompromised woman developed acute left eye blindness and paraparesis suspected to be due to neuromyelitis optica (NMO). During treatment for NMO, right eye blindness and progressive multiple cranial neuropathies developed. Cerebrospinal fluid polymerase chain reaction (PCR) revealed Varicella zoster virus (VZV). This case emphasizes the importance of considering VZV in individuals, particularly the immunocompromised, presenting with a constellation of neurological signs and symptoms, even in the absence of rash.

Potential Predictors of Poor Visual Outcome in Human Leukocyte Antigen-B27-Associated Uveitis.

PURPOSE: To identify potential predictors of permanent vision loss in patients with human leukocyte antigen (HLA)-B27-associated uveitis in a tertiary referral center. DESIGN: Retrospective case-control study. METHODS: The charts of 212 patients (338 eyes) with HLA-B27-associated uveitis that visited the University Medical Center Utrecht with a follow-up of at least 6 months were retrospectively studied. Clinical features at presentation and during follow-up were compared to final visual outcome in quiescent state. Eyes with (sub-) normal vision (>20/50) were compared with visually impaired (≤20/50) and blind (≤5/50, or a visual field of <10 degrees) eyes, using survival analysis. A multivariate Cox proportional hazards analysis was performed to analyze potential predictors for permanent vision loss. RESULTS: Median follow-up was 10.4 years (range, 0.5-44.7 years). During follow-up 226 eyes (66%) experienced vision loss up to 20/50, but most recovered. Twenty patients (9%) became permanently visually impaired or blind in at least 1 eye because of uveitis, after a median of 9.7 years (range, 0-20.9 years). The main cause was secondary glaucoma or related to glaucoma surgery (12/22 eyes, 55%). Survival analysis showed, after adjustment for age and sex, an ocular pressure of >21 mm Hg, hypotony, and panuveitis to be potential predictors at presentation, and the development of secondary glaucoma or hypotony to be predictors of blindness or visual impairment during follow-up. CONCLUSIONS: The long-term visual prognosis of HLA-B27-associated uveitis is relatively good, but the true incidence of permanent vision loss is probably still underestimated. Our findings highlight the importance of proper control of intraocular pressure.

Generation of novel monoclonal antibodies for the enrichment and characterization of human corneal endothelial cells (hCENC) necessary for the treatment of corneal endothelial blindness.

Corneal transplantation is the primary treatment option to restore vision for patients with corneal endothelial blindness. Although the success rate of treatment is high, limited availability of transplant grade corneas is a major obstacle. Tissue-engineered corneal endothelial grafts constructed using cultivated human corneal endothelial cells (hCENC) isolated from cadaveric corneas may serve as a potential graft source. Currently, tools for the characterization of cultured hCENC and enrichment of hCENC from potential contaminating cells such as stromal fibroblasts are lacking. In this study, we describe the generation and characterization of novel cell surface monoclonal antibodies (mAbs) specific for hCENC. These mAbs could be used for enrichment and characterization of hCENC. Out of a total of 389 hybridomas, TAG-1A3 and TAG-2A12 were found to be specific to the corneal endothelial monolayer by immunostaining of frozen tissue sections. Both mAbs were able to clearly identify hCENC with good 'cobblestone-like' morphology from multiple donors. The antigen targets for TAG-1A3 and TAG-2A12 were found to be CD166/ALCAM and Peroxiredoxin-6 (Prdx-6), respectively, both of which have not been previously described as markers of hCENC. Additionally, unlike other Prdx-6 mAbs, TAG-2A12 was found to specifically bind cell surface Prdx-6, which was only expressed on hCENC and not on other cell types screened such as human corneal stromal fibroblasts (hCSF) and human pluripotent stem cells (hPSC). From our studies, we conclude that TAG-1A3 and TAG-2A12 are promising tools to quantitatively assess hCENC quality. It is also noteworthy that the binding specificity of TAG-2A12 could be used for the enrichment of hCENC from cell mixtures of hCSF and hPSC.

Sphenoid sinus dehiscence as a risk for visual consequences in an immunocompromised patient.

Isolated sphenoid sinus disease is a rare entity with severe and potentially life threatening sequela. Because of the proximity of the sinus to the orbit, anatomical defects within the surrounding bony structures can facilitate communication with orbital content, predisposing the patient to substantial visual consequences. We report a case of a 51-year-old immunocompromised male who presented with headache and gradual unilateral decreases in vision. Computed tomography revealed opacification of the left sphenoid sinus accompanied by unusual bony dehiscence of the proximal optic canal. Early recognition and treatment of sphenoid sinusitis requires urgent surgical intervention with delay of treatment potentially leading to irreversible blindness or other devastating consequences. Bony dehiscence of the sphenoid sinus overlying the optic nerve has only been found in 4% of cadavers. It is associated with increased risk of orbital complications and predicts a poor prognosis. Immediate intervention is particularly important in immunocompromised individuals who are at greater risk of these severe complications.

Vernal keratoconjunctivitis: a severe allergic eye disease with remodeling changes.

Vernal keratoconjunctivitis (VKC) is an unusually severe sight-threatening allergic eye disease, occurring mainly in children. Conventional therapy for allergic conjunctivitis is generally not adequate for VKC. Pediatricians and allergists are often not familiar with the severe clinical symptoms and signs of VKC. As untreated VKC can lead to permanent visual loss, pediatric allergists should be aware of the management and therapeutic options for this disease to allow patients to enter clinical remission with the least side effects and sequelae. Children with VKC present with severe ocular symptoms, that is, severe eye itching and irritation, constant tearing, red eye, eye discharge, and photophobia. On examination, giant papillae are frequently observed on the upper tarsal conjunctiva (cobblestoning appearance), with some developing gelatinous infiltrations around the limbus surrounding the cornea (Horner-Trantas dot). Conjunctival injections are mostly severe with thick mucus ropy discharge. Eosinophils are the predominant cells found in the tears and eye discharge. Common therapies include topical antihistamines and dual-acting agents, such as lodoxamide and olopatadine. These are infrequently sufficient and topical corticosteroids are often required for the treatment of flare ups. Ocular surface remodeling leads to severe suffering and complications, such as corneal ulcers/scars. Other complications include side effects from chronic topical steroids use, such as increased intraocular pressure, glaucoma, cataract and infections. Alternative therapies for VKC include immunomodulators, such as cyclosporine A and tacrolimus. Surgery is reserved for those with complications and should be handled by ophthalmologists with special expertise. Newer research on the pathogenesis of VKC is reviewed in this article. Vernal keratoconjunctivitis is a very important allergic eye disease in children. Complications and remodeling changes are unique and can lead to blindness. Understanding of pathogenesis of VKC may lead to better therapy for these unfortunate patients.

False-positive anti-retinal antibodies as a cause of psychogenic vision loss.

PURPOSE: To report a case of psychogenic vision loss caused by false-positive anti-retinal antibody testing. METHODS: We describe a case of visual and systemic symptoms following anti-retinal antibody detection. The case was analyzed for clinical presentation, diagnosis, and consequences of false-positive testing. RESULTS: The patient presented with decreased vision without detectable pathology on ophthalmic examination. Tests were ordered in search of a diagnosis, including an antibody test. Following detection of anti-retinal antibodies, the patient developed worsening visual symptoms and systemic manifestations. A repeat antibody test performed at our institution revealed negative results, which, in conjunction with lack of visual field expansion, confirmed our suspicion of psychogenic vision loss. CONCLUSIONS: Laboratory screening may be limited by test specificity and can lead to false-positive results, affecting the patient psychologically and clinically. Care must be taken in patients with positive anti-retinal antibodies to ensure the presence of definitive disease before initiation of treatment.

Immunology of age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population.

Evaluation of ocular manifestations and blindness in HIV/AIDS patients in a tertiary care hospital in South India.

PURPOSE: To report the prevalence of ocular manifestations in patients with HIV/AIDS and their correlation with the clinical stage of disease as well as the CD4 cell count. METHODS: 100 HIV-positive patients, who presented to a tertiary care hospital, were included. The WHO clinical staging of HIV/AIDS, CD4 count, duration of disease, and presence and type of ocular manifestations were noted. RESULTS: Overall, 46 patients (46%) had ocular manifestations related to HIV/AIDS. The most common manifestations were HIV retinopathy (12%) and cytomegalovirus (CMV) retinitis (7%). The prevalence of ocular manifestations correlated significantly with the WHO clinical stages 3 and 4 of HIV/AIDS (p = .001) and with low CD4 count (p = .001). CONCLUSIONS: CD4 cell counts and WHO clinical stage of HIV disease are important predictors for the occurrence of ocular morbidity in HIV-positive individuals. Routine comprehensive ophthalmic screening and appropriate initiation of therapy in these patients can potentially decrease ocular morbidity.

Galectin-1 reduces the severity of herpes simplex virus-induced ocular immunopathological lesions.

Stromal keratitis is a chronic immunopathological lesion of the eye caused by HSV-1 infection that can result in blindness. Because the inflammatory lesions are primarily orchestrated by Th1 cells, and to a lesser extent by Th17 cells, inhibiting their activity represents a useful form of therapy. In this study we evaluated the therapeutic potential of galectin-1 (gal-1), an endogenous lectin that in some autoimmune diseases was shown to suppress the functions of Th1 and Th17 cells. Treatment was begun at different times after ocular infection with HSV and the outcome was assessed clinically as well as for effects on various immune parameters. Treatment with recombinant gal-1 significantly diminished stromal keratitis lesion severity and the extent of corneal neovascularization. Treated mice had reduced numbers of IFN-γ- and IL-17-producing CD4(+) T cells, as well as neutrophil infiltration in the cornea. Furthermore, disease severity was greater in gal-1 knockout mice compared with their wild-type counterparts. The many effects of gal-1 treatment include reduction in the production of proinflammatory cytokines and chemokines, increased production of IL-10, and inhibitory effects on molecules involved in neovascularization. To our knowledge, our findings are the first to show that gal-1 treatment represents a useful approach to control lesion severity in a virally induced immunopathological disease.

Opposing roles for CXCR3 signaling in central nervous system versus ocular inflammation mediated by the astrocyte-targeted production of IL-12.

CXCR3 and its ligands are important for the trafficking of activated CD4(+) T(H)1 T cells, CD8(+) T cells, and natural killer cells during inflammation. Recent functional studies demonstrate a more diverse role of CXCR3 in inflammatory diseases of the central nervous system (CNS). We examined the impact of CXCR3 on a less complex interferon-γ-dependent, type 1 cell-mediated immune response in the CNS, induced in mice by the transgenic production of glial fibrillary acidic protein IL-12 (GF-IL12) by astrocytes and retinal Müller cells. GF-IL12 mice develop ataxia because of severe cerebellar inflammation but have little overt ocular disease. Surprisingly, CXCR3-deficient GF-IL12 mice (GF-IL12/CXCR3KO) have drastically reduced ataxia but developed cataracts, severe ocular inflammation, and eye atrophy. Most GF-IL12/CXCR3KO mice had minimal cerebellar inflammation but severe retinal disorganization, loss of photoreceptors, and lens destruction in the eye. The number of CD3(+), CD11b(+), and natural killer 1.1(+) cells were reduced in the CNS but highly increased in the eyes of GF-IL12/CXCR3KO compared with GF-IL12 mice. High levels of interferon-γ, IL-1, tumor necrosis factor α, CXCL9, CXCL10, and CCL5 were found in GF-IL12 cerebelli and GF-IL12/CXCR3KO eyes. Our findings demonstrate key but paradoxical functions for CXCR3 in IL-12-induced immune disease in the CNS, promoting inflammation in the brain yet restricting it in the eye. We conclude that the function of CXCR3 in cellular immune disease is driven by a common trigger and is controlled by tissue-specific factors.

[Therapy for childhood uveitis: biologics: too often--too late?]. / Uveitistherapie im Kindesalter: Biologika: zu oft--zu spät?

Pediatric uveitis differs from uveitis seen in adulthood not only because of the uveitis presentation and severity of disease but also by a worse prognosis and age-specific problems that may occur under therapy. Biologics are selective acting proteins that are manufactured by biotechnology. The greatest amount of knowledge to date exists for the TNF alpha blocking agents. Experimental and clinical studies showed that TNF alpha plays a significant role in the process of intraocular inflammation, so it was a logical step to use TNF blocking agents in uveitis therapy. Randomized controlled studies are rare, but pooled data (as presented here) of case series published show good evidence for the efficacy especially of infliximab and adalimumab. It is to be hoped that blindness and severe sight disabilities can be further reduced by this treatment in the future. From pediatric rheumatology we have learned about even newer biologics. With this review we want to show the weaknesses and strengths of therapy with biologics and want to help in choosing this treatment at the indicated time point in the disease.

Orbital apex syndrome secondary to mucormycosis after a tooth extraction in an immunocompetent patient.

Mucormycosis is rare in immunocompetent patients. We describe an unusual case of orbital apex syndrome secondary to mucormycosis that occurred in an immunocompetent 64-year-old man following multiple tooth extractions. We found no frank involvement of the maxillary sinus, which is the usual pathway of spread for this fungal infection. Therefore, we suggest two possible alternate pathways from the oral mucosa to the orbital apex: one via the anterosuperior and posterosuperior alveolar vessels and one via the infraorbital branch of the maxillary artery.